Maria Benevolo1, Pamela Mancuso2, Elena Allia3, Daniela Gustinucci4, Simonetta Bulletti4, Elena Cesarini4, Francesca Maria Carozzi5, Massimo Confortini5, Simonetta Bisanzi5, Gabriele Carlinfante6, Teresa Rubino6, Francesca Rollo1, Natalina Marchi7, Angelo Farruggio7, Teresa Pusiol8, Francesco Venturelli2,9, Paolo Giorgi Rossi2. 1. Pathology Department, IRCCS Regina Elena National Cancer Institute, Rome, Italy. 2. Epidemiology Unit, Azienda Unità Sanitaria Locale-IRCCS of Reggio Emilia, Reggio Emilia, Italy. 3. Centre for Cervical Cancer Screening, City of Health and Science Hospital, Turin, Italy. 4. Laboratory Screening Unit, Local Health Authority-Umbria 1, Perugia, Italy. 5. Regional Laboratory of Cancer Prevention, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy. 6. Cervico-Vaginal Cytology Unit, Azienda Unità Sanitaria Locale-IRCCS of Reggio Emilia, Reggio Emilia, Italy. 7. Unit 17, Local Health and Social Care Facility, Este-Monselice, Italy. 8. Screening Cervical Cancer Prevention Laboratory, Institute of Anatomic Pathology, Rovereto Hospital, Rovereto, Italy. 9. Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy.
Abstract
BACKGROUND: p16/Ki-67 dual staining is a candidate biomarker for triaging human papillomavirus (HPV)-positive women. Reproducibility is needed for adopting a test for screening. This study assessed interlaboratory reproducibility in HPV-positive women. METHODS: All women positive for HPV from the Italian New Technologies for Cervical Cancer 2 study, were included in this study. ThinPrep slides were immunostained for p16/Ki-67 in 4 laboratories and were interpreted in 7 laboratories. Each slide had 3 reports from different laboratories. Slides were classified as valuable or inadequate, and valuable slides were classified as positive (at least 1 double-stained cell) or negative. Interlaboratory reproducibility was evaluated with κ values. RESULTS: Overall, we obtained 9300 reports for 3100 cases; 905 reports (9.7%) were inadequate. The overall adequacy concordance was poor (κ = 0.224; 95% confidence interval [CI], 0.183-0.263). The overall positivity concordance was moderate (κ = 0.583; 95% CI, 0.556-0.610). Of the 176 cervical intraepithelial neoplasia 2+ (CIN-2+) lesions found in HPV DNA-positive women, 158 had a valid result: 107 were positive in all 3 reports (sensitivity for CIN-2+, 67.7%; 95% CI, 59.8%-74.9%), 23 were positive in 2 reports (sensitivity of the majority report, 82.3%; 95% CI, 75.4%-87.9%), and 15 were positive in 1 report (sensitivity of at least 1 positive result, 91.8%; 95% CI, 86.3%-95.5%). Thirteen CIN-2+ cases were negative in all 3 reports. The overall positivity concordance in CIN-2+ samples was κ = 0.487 (95% CI, 0.429-0.534), whereas in the non-CIN-2+ samples, it was κ = 0.558 (95% CI, 0.528-0.588). CONCLUSIONS: The p16/Ki-67 assay showed poor reproducibility for adequacy and good reproducibility for positivity comparable to that of cervical cytology. Nevertheless, the low reproducibility does not affect the sensitivity for CIN-2+.
BACKGROUND:p16/Ki-67 dual staining is a candidate biomarker for triaging human papillomavirus (HPV)-positive women. Reproducibility is needed for adopting a test for screening. This study assessed interlaboratory reproducibility in HPV-positive women. METHODS: All women positive for HPV from the Italian New Technologies for Cervical Cancer 2 study, were included in this study. ThinPrep slides were immunostained for p16/Ki-67 in 4 laboratories and were interpreted in 7 laboratories. Each slide had 3 reports from different laboratories. Slides were classified as valuable or inadequate, and valuable slides were classified as positive (at least 1 double-stained cell) or negative. Interlaboratory reproducibility was evaluated with κ values. RESULTS: Overall, we obtained 9300 reports for 3100 cases; 905 reports (9.7%) were inadequate. The overall adequacy concordance was poor (κ = 0.224; 95% confidence interval [CI], 0.183-0.263). The overall positivity concordance was moderate (κ = 0.583; 95% CI, 0.556-0.610). Of the 176 cervical intraepithelial neoplasia 2+ (CIN-2+) lesions found in HPV DNA-positive women, 158 had a valid result: 107 were positive in all 3 reports (sensitivity for CIN-2+, 67.7%; 95% CI, 59.8%-74.9%), 23 were positive in 2 reports (sensitivity of the majority report, 82.3%; 95% CI, 75.4%-87.9%), and 15 were positive in 1 report (sensitivity of at least 1 positive result, 91.8%; 95% CI, 86.3%-95.5%). Thirteen CIN-2+ cases were negative in all 3 reports. The overall positivity concordance in CIN-2+ samples was κ = 0.487 (95% CI, 0.429-0.534), whereas in the non-CIN-2+ samples, it was κ = 0.558 (95% CI, 0.528-0.588). CONCLUSIONS: The p16/Ki-67 assay showed poor reproducibility for adequacy and good reproducibility for positivity comparable to that of cervical cytology. Nevertheless, the low reproducibility does not affect the sensitivity for CIN-2+.
Authors: Giorgio Bogani; Luca Lalli; Francesco Sopracordevole; Andrea Ciavattini; Alessandro Ghelardi; Tommaso Simoncini; Francesco Plotti; Jvan Casarin; Maurizio Serati; Ciro Pinelli; Alice Bergamini; Barbara Gardella; Andrea Dell'Acqua; Ermelinda Monti; Paolo Vercellini; Innocenza Palaia; Giorgia Perniola; Margherita Fischetti; Giusi Santangelo; Alice Fracassi; Giovanni D'Ippolito; Lorenzo Aguzzoli; Vincenzo Dario Mandato; Luca Giannella; Cono Scaffa; Francesca Falcone; Chiara Borghi; Mario Malzoni; Andrea Giannini; Maria Giovanna Salerno; Viola Liberale; Biagio Contino; Cristina Donfrancesco; Michele Desiato; Anna Myriam Perrone; Giulia Dondi; Pierandrea De Iaco; Simone Ferrero; Giuseppe Sarpietro; Maria G Matarazzo; Antonio Cianci; Stefano Cianci; Sara Bosio; Simona Ruisi; Lavinia Mosca; Raffaele Tinelli; Rosa De Vincenzo; Gian Franco Zannoni; Gabriella Ferrandina; Marco Petrillo; Giampiero Capobianco; Salvatore Dessiole; Annunziata Carlea; Fulvio Zullo; Barbara Muschiato; Stefano Palomba; Stefano Greggi; Arsenio Spinillo; Fabio Ghezzi; Nicola Colacurci; Roberto Angioli; Pierluigi Benedetti Panici; Ludovico Muzii; Giovanni Scambia; Francesco Raspagliesi; Violante Di Donato Journal: Vaccines (Basel) Date: 2022-04-09
Authors: Anne Hammer; Line W Gustafson; Pia N Christensen; Rikke Brøndum; Berit Andersen; Rikke H Andersen; Mette Tranberg Journal: Cancer Med Date: 2020-09-07 Impact factor: 4.452